Merck Sharp + Dohme Corp.

Emily Wen

Michael Albert Winters

Patrick McHugh

Patrick L Ahl

Akhilesh Bhambhani

Jessica Sinacola

Matthew P Watson

Morrisa C Jones

Justin Stanbro

Christopher Jon Farrell

Daniel D Roth

Jian He

Jitin Bajaj

John M Williams

Chitrananda Abeygunawardana

Luwy Kavuka Musey

Joseph G Joyce

Julie Marie Skinner

William J Smith

John E MacNair

Catherine Lancaster

Hari Pujar

Patrick Mchugh

Patrick Leonard Ahl

Jessica R Sinacola

A method is described for producing a pneumococcal capsular polysaccharide protein conjugate in which one or more activated pneumococcal polysaccharides of particular pneumococcal serotypes and carrier protein are separately lyophilized, the separately lyophilized polysaccharides and carrier protein are separately reconstituted in an organic solvent, and the reconstituted polysaccharide and carrier protein are then combined together by Tee-mixing and conjugated together to produce polysaccharide carrier protein conjugates. A plurality of conjugates, each comprising polysaccharides of a particular serotype, may be used to produce multivalent pneumococcal immunogenic compositions having a combination of conjugates for use in vaccines.

Methods for producingcapsular polysaccharide carrier protein conjugates

A method is described for producing a pneumococcal capsular polysaccharide protein conjugate in which one or more activated pneumococcal polysaccharides of particular pneumococcal serotypes and carrier protein are separately lyophilized in the form of lyospheres of carrier protein and lyospheres of the one or more polysaccharides. A predetermined amount of carrier protein lyospheres and activated polysaccharide lyospheres are mixed together and the mixture reconstituted in an organic solvent to produce polysaccharide carrier protein conjugates. A plurality of conjugates, each comprising polysaccharides of a particular serotype, may be used to produce multivalent pneumococcal immunogenic compositions having a combination of conjugates for use in vaccines.

Methods for producing streptococcus pneumoniae capsular polysaccharide carrier protein conjugates from lyospheres

The present invention provides methods for making polysaccharide-protein conjugates in which polysaccharides, typically from bacteria, are conjugated to a carrier protein by reductive amination under conditions which improve conjugation reaction consistency, increase consumption of protein during conjugation reaction, generate conjugates of higher molecular weight, and/or reduce the levels of free cyanide in the conjugate reaction product. The polysaccharide-protein conjugates obtained using these methods are useful for inclusion in multivalent vaccines.

Methods for making polysaccharide-protein conjugates

A method is described for reconstituting lyophilized mutant diphtheria toxin in dimethyl sulfoxide for use in producing pneumococcal capsular polysaccharide mutant diphtheria toxin conjugates.

Methods for providing a homogenous solution of lyophilized mutant diptheria toxin in dimethylsulfoxide

The present invention provides immunogenic compositions having one or more polysaccharide-protein conjugates in which one or more polysaccharides frombacterial capsules are conjugated to a carrier protein in an aprotic solvent such as dimethylsulfoxide (DMSO). The present invention also provides methods for providing an enhanced immune response to a pneumococcal polysaccharide protein conjugate vaccine comprising administering to a human subject an immunogenic composition comprising polysaccharide-protein conjugates prepared in DMSO conditions.

Enhancing immunogenicity ofpolysaccharide-protein conjugates

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Harleysville, PA, United States of America

Emily Wen